Achieving Molecular Remission before Allogeneic Stem Cell Transplantation in Adult Patients with Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia: Impact on Relapse and Long-Term Outcome

Federico Lussana, Tamara Intermesoli, Francesca Gianni, Cristina Boschini, Arianna Masciulli, Orietta Spinelli, Elena Oldani, Manuela Tosi, Anna Grassi, Margherita Parolini, Ernesta Audisio, Chiara Cattaneo, Roberto Raimondi, Emanuele Angelucci, Irene Maria Cavattoni, Anna Maria Scattolin, Agostino Cortelezzi, Francesco Mannelli, Fabio Ciceri, Daniele MatteiErika Borlenghi, Elisabetta Terruzzi, Claudio Romani, Renato Bassan, Alessandro Rambaldi

Research output: Contribution to journalArticle

Abstract

Allogeneic stem cell transplantation (alloHSCT) in first complete remission (CR1) remains the consolidation therapy of choice in Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL). The prognostic value of measurable levels of minimal residual disease (MRD) at time of conditioning is a matter of debate. We analyzed the predictive relevance of MRD levels before transplantation on the clinical outcome of Ph+ ALL patients treated with chemotherapy and imatinib in 2 consecutive prospective clinical trials. MRD evaluation before transplantation was available for 65 of the 73 patients who underwent an alloHSCT in CR1. A complete or major molecular response at time of conditioning was achieved in 24 patients (37%), whereas 41 (63%) remained carriers of any other positive MRD level in the bone marrow. MRD negativity at time of conditioning was associated with a significant benefit in terms of risk of relapse at 5 years, with a relapse incidence of 8% compared with 39% for patients with MRD positivity (P = .007). However, thanks to the post-transplantation use of tyrosine kinase inhibitors (TKIs), disease-free survival was 58% versus 41% (P = .17) and overall survival was 58% versus 49% (P = .55) in MRD-negative compared with MRD-positive patients, respectively. The cumulative incidence of nonrelapse mortality was similar in the 2 groups. Achieving a complete molecular remission before transplantation reduces the risk of leukemia relapse even though TKIs may still rescue some patients relapsing after transplantation.

Original languageEnglish
Pages (from-to)1983-1987
Number of pages5
JournalBiology of Blood and Marrow Transplantation
Volume22
Issue number11
DOIs
Publication statusPublished - Nov 1 2016

Keywords

  • Acute lymphoblastic leukemia
  • Allogeneic transplantation
  • Minimal residual disease (MRD)

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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    Lussana, F., Intermesoli, T., Gianni, F., Boschini, C., Masciulli, A., Spinelli, O., Oldani, E., Tosi, M., Grassi, A., Parolini, M., Audisio, E., Cattaneo, C., Raimondi, R., Angelucci, E., Cavattoni, I. M., Scattolin, A. M., Cortelezzi, A., Mannelli, F., Ciceri, F., ... Rambaldi, A. (2016). Achieving Molecular Remission before Allogeneic Stem Cell Transplantation in Adult Patients with Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia: Impact on Relapse and Long-Term Outcome. Biology of Blood and Marrow Transplantation, 22(11), 1983-1987. https://doi.org/10.1016/j.bbmt.2016.07.021